The Role of MHC Class I Expression in Rat NK Cell-Mediated Lysis of Syngeneic Tumor Cells and Virus-Infected Cells

Abstract

In this study the role of MHC class I antigen expression in rat natural killer (NK) cellmediated lysis was investigated. Various rat tumor cell lines and two Adenovirus (Ad)transformed rat cell lines were tested for their expression levels of total MHC class I and two MHC class I alleles, RT1.A and RT1.C, by flow cytometry. Their susceptibility to NK cell-mediated lysis in relation to MHC class I expression was determined by 51Cr release assays. IFN-γ is know to increase the expression of MHC class I. Therefore target cell with and without prior IFN-γ treatment were examined for MHC class I expression and its effect on NK lysis. An significant inverse exponential relationship was found. To investigate the effect of virus infection on MHC class I expression and target cell lysis by NK cells, rat embryonal fibroblasts (REF) were infected with cytomegalovirus (CMV) and used as target cells for NK cell-mediated lysis. Results showed that these virus-infected cells were less susceptible to NK lysis than non-infected cells. Moreover, the non-infected cells expressed less MHC class I than the infected cells, indicating that also in this case, there was an inverse correlation between MHC class I expression and susceptibility to lysis by NK cells. Subsequently, we showed that sorted subsets of predominantly CD8-positive and CD8-negative NK cells lysed a MHC class I-positive tumor cell line at the same level. This suggests that CD8 is not likely to participate as a receptor for MHC class I in NK cell-mediated lysis in a syngeneic rat model.